Molecular signatures of amyotrophic lateral sclerosis disease progression in hind and forelimb muscles of an SOD1(G93A) mouse model.

Antioxidants & Redox Signaling
Daniele CapitanioCecilia Gelfi

Abstract

This study utilized proteomics, biochemical and enzymatic assays, and bioinformatics tools that characterize protein alterations in hindlimb (gastrocnemius) and forelimb (triceps) muscles in an amyotrophic lateral sclerosis (ALS) (SOD1(G93A)) mouse model. The aim of this study was to identify the key molecular signatures involved in disease progression. Both muscle types have in common an early down-regulation of complex I. In the hindlimb, early increases in oxidative metabolism are associated with uncoupling of the respiratory chain, an imbalance of NADH/NAD(+), and an increase in reactive oxygen species (ROS) production. The NADH overflow due to complex I inactivation induces TCA flux perturbations, leading to citrate production, triggering fatty acid synthase (FAS), and lipid peroxidation. These early metabolic changes in the hindlimb followed by sustained and comparatively higher metabolic and cytoskeletal derangements over time precede and may catalyze the progressive muscle wasting in this muscle at the late stage. By contrast, in the forelimb, there is an early down-regulation of complexes I and II that is associated with the reduction of oxidative metabolism, which promotes metabolic homeostasis that is accompanied by ...Continue Reading

References

Jun 1, 1992·The Journal of Histochemistry and Cytochemistry : Official Journal of the Histochemistry Society·B W RosserP M Nemeth
Jul 31, 1986·Biochemical and Biophysical Research Communications·D Danieli BettoR Betto
Dec 1, 1996·Proceedings of the Society for Experimental Biology and Medicine·E E Dupont-VersteegdenR J McCarter
Jun 23, 1997·FEBS Letters·S NarumiyaN Watanabe
Sep 18, 2003·Amyotrophic Lateral Sclerosis and Other Motor Neuron Disorders : Official Publication of the World Federation of Neurology, Research Group on Motor Neuron Diseases·Michael Strong, Jeffrey Rosenfeld
Jan 23, 2004·Experimental Neurology·Lindsey R FischerJonathan D Glass
Aug 18, 2004·Trends in Molecular Medicine·Caterina Bendotti, Maria Teresa Carrì
Feb 17, 2006·Neurology·G M PasinettiL Ho
Mar 31, 2006·Molecular & Cellular Proteomics : MCP·Thomas J LukasTeepu Siddique
Jun 3, 2006·European Journal of Cell Biology·Atsuo T Sasaki, Richard A Firtel
Aug 25, 2006·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Thomas W GouldRonald W Oppenheim
Oct 21, 2006·Proceedings of the National Academy of Sciences of the United States of America·Marco SandriBruce M Spiegelman
Jan 2, 2007·Biochemical and Biophysical Research Communications·Tania MassignanValentina Bonetto
Mar 3, 2007·Clinical Chemistry·Antoon J M JanssenRichard J T Rodenburg
Apr 4, 2007·Genes & Development·Christoph HandschinBruce M Spiegelman
Apr 18, 2007·Journal of Lipid Research·Anissa FerganiJean-Philippe Loeffler
Nov 15, 2007·Physiological Genomics·Jose-Luis Gonzalez de AguilarJean-Philippe Loeffler
Feb 22, 2008·Journal of Cell Science·Verena KölschRichard A Firtel
Jun 17, 2008·Science·Ann-Hwee LeeLaurie H Glimcher
Dec 9, 2008·The Biochemical Journal·Michael P Murphy
Jan 1, 2009·Mass Spectrometry Reviews·Martin H Maurer
Jan 23, 2009·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Suh Young JeongSamuel David
Feb 5, 2009·Orphanet Journal of Rare Diseases·Lokesh C Wijesekera, P Nigel Leigh
Mar 24, 2009·Journal of Neurology·C BouteloupP Couratier
Apr 24, 2009·Current Opinion in Pharmacology·Luc Dupuis, Jean-Philippe Loeffler
May 15, 2009·American Journal of Physiology. Cell Physiology·Peter J AdhihettyDavid A Hood
Jun 23, 2009·Current Opinion in Neurobiology·R Jeroen Pasterkamp, Roman J Giger

❮ Previous
Next ❯

Citations

Jun 20, 2013·Expert Review of Proteomics·Ashling Holland, Kay Ohlendieck
May 23, 2015·Amyotrophic Lateral Sclerosis & Frontotemporal Degeneration·Renaid B KimCassie S Mitchell
Feb 28, 2016·Journal of Neuropathology and Experimental Neurology·Sonja KörnerSusanne Petri
Dec 11, 2014·Annals of Clinical and Translational Neurology·Ying SiPeter H King
Jan 19, 2016·Brain Pathology·Jean-Philippe LoefflerJose-Luis Gonzalez De Aguilar
Jun 5, 2014·Proteomics. Clinical Applications·Heinrich Brinkmeier, Kay Ohlendieck
Oct 24, 2014·Frontiers in Cellular Neuroscience·Trisha R Stankiewicz, Daniel A Linseman
Aug 16, 2016·Biochemical and Biophysical Research Communications·Swati AgarwalRajnish Kumar Chaturvedi
Jun 18, 2017·Life Sciences·Daniela Recabarren, Marcelo Alarcón
Jan 21, 2014·Cellular and Molecular Neurobiology·Gabriela P de OliveiraGerson Chadi
Aug 7, 2017·Expert Review of Proteomics·Daniele CapitanioCecilia Gelfi
Oct 31, 2017·Mediators of Inflammation·Alberto Ferri, Roberto Coccurello
Jul 5, 2016·Expert Review of Proteomics·Paul DowlingKay Ohlendieck
Nov 12, 2018·Journal of Molecular Neuroscience : MN·Efthimios DardiotisAristidis Tsatsakis
Aug 11, 2018·Molecular Neurodegeneration·Giovanni NardoCaterina Bendotti
Jun 20, 2019·Frontiers in Neuroscience·Gavin PharaohHolly Van Remmen
Jan 18, 2018·Expert Review of Proteomics·Sandra MurphyKay Ohlendieck
Oct 31, 2017·Mediators of Inflammation·Massimo TortaroloCaterina Bendotti
Jun 28, 2019·Frontiers in Neuroscience·Thomas J HedlAlbert Lee
Apr 4, 2017·Magnetic Resonance in Medicine : Official Journal of the Society of Magnetic Resonance in Medicine·Pietro BontempiPasquina Marzola
Jan 27, 2019·Archives of Biochemistry and Biophysics·Jingsong ZhouJianxun Yi

❮ Previous
Next ❯

Methods Mentioned

BETA
transgenic
electrophoresis
protein folding
PCR

Software Mentioned

GeneGo
Image Quant TL
ImageQuant
MetaCore

Related Concepts

Related Feeds

Amyloid Lateral Sclerosis

Amyotrophic Lateral Sclerosis (ALS) is a progressive nervous system disease associated with the death of neurons that control voluntary muscles. Discover the latest research on ALS here.

AKT Pathway

This feed focuses on the AKT serine/threonine kinase, which is an important signaling pathway involved in processes such as glucose metabolism and cell survival.

ALS: Genetics

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder characterized by muscle weakness. Here is the latest research investigating genetic alterations in this genetically heterogeneous disorder.

ALS: Genetics

Amyotrophic Lateral Sclerosis (ALS) is a progressive neurodegenerative disorder characterized by muscle weakness. ALS is a genetically heterogeneous disorder with several causative genes. Here are the latest discoveries pertaining to the genetics of this disease.